Venous Microangiopathy Research Articles

Video-capillaroscopy, a promising tool for the clinical evaluation of patients with chronic venous insufficiency.

The cutaneous microangiopathy plays a key role in the development of the skin clinical lesions of venous insufficiency. Capillaroscopy allows a non-invasive observation of the superficial skin capillaries of the lower leg, which have previously been shown to be altered in patients with advanced venous disease. As it is now available in a friendly, easy to handle way through modern video devices, we report our findings in a short series of patients with C3-C5 chronic venous disorders using this technique. A total of 21 patients with venous insufficiency (C3-C5 on at least one leg) underwent a capillaroscopic examination of both legs and pictures recorded from the sites of the most severe venous skin lesions. This was performed with a CapXview handheld video-capillaroscope (×100 magnification), allowing easy manual measurement of maximum capillary bulk diameter and capillary density. Dramatic changes in capillary density, size, and shape were easily observed at the site of the venous skin lesions. A significant negative linear relationship was found between capillary density and the "C" classes (r = -0.45; P < 0.001). A significant negative correlation was also found between capillary density and bulk diameter (r = -0.52; P < 0.001). The area under the ROC curve for the mathematical prediction of venous skin changes by capillary density was 0.842, which shows the strength of the link between the microvascular and the clinical status. Video-capillaroscopy allows a direct observation of the cutaneous venous microangiopathy and provides the possibility to measure capillary density which allows its quantification. This simple to use technique shows the potential for a more precise follow-up and treatment evaluation of the cutaneous consequences of venous disease, which remains to be further investigated.

Hypertension pulmonaire et connectivites

Pulmonary hypertension (PH) is a rare complication of connective tissue diseases (CTD), and especially of systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). It is defined by an elevation of mean pulmonary arterial pressure above 25mmHg documented during a right-heart catheterization. Due to their systemic nature, CTD can induce PH by several mechanisms, that are sometimes intricated: pulmonary arterial (group 1) or venous (groupe 1′) microangiopathy, left-heart disease (group 2), chronic lung disease (group 3) and/or chronic thromboembolic disease (group 4). PH suspicion is often raised by echocardiographic data (which can show an elevation of the tricuspid regurgitation jet and/or a right atrial dilation), and/or by an isolated decrease in DLCO observed during pulmonary function tests, an unexplained elevation of serum NT-pro-BNP or right-heart abnormalities on an electrocardiogram. Its formal diagnosis always requires a hemodynamic confirmation by right-heart catheterization. Therapeutic management of PH depends of the underlying mechanism(s): pulmonary vasodilators in group 1 PH (with possible use of immunosuppressants in case of SLE or MCTD); management of an underlying left-heart disease in group 2 PH; management of an underlying chronic lung disease in group 3 PH; anticoagulation, pulmonary vasodilators, pulmonary endartectomy or balloon pulmonary angioplasty in group 4 PH. Regular follow-up is mandatory in patients with PH and CTD.

Five-year treatment of chronic venous insufficiency with O-(β-hydroxyethyl)-rutosides: Safety aspects

Chronic venous insufficiency (CVI), and related signs and symptoms of venous and diabetic microangiopathy, can be effectively treated with O-(β-hydroxyethyl)-rutosides (HR). The aim of the present independent registry study was to evaluate HR in a long-term (five-year) period of administration that examined the tolerability and safety of HR. Patients with severe CVI and venous microangiopathy were included in the registry. Subjects who completed five years of treatment were considered in the analysis. Blood parameters, liver and renal function tests, microalbuminuria (in diabetic patients) and cholesterol levels were evaluated to assess the effects of HR treatment. Four groups were studied - group A (98 patients) received oral HR (1500 mg per day), group B (87 diabetic patients with CVI) was treated with 2 g of HR per day, group C (90 controls, including 42 diabetic patients) had no pharmacological treatment and group D (113 patients, including 48 diabetic patients) used elastic stockings. No significant negative changes in blood parameters were recorded at two and five years. Decreases in microalbuminuria and total cholesterol, and an increase in high-density lipoprotein cholesterol were observed in HR-treated patients, particularly in diabetic patients. Minimal (nonsignificant) variations were observed in the groups that did not use HR. In conclusion, HR treatment is safe, and some positive effects from HR on cholesterol levels and microalbuminuria (in diabetic patients) that were previously observed may suggest potential new clinical applications.

O-(β-Hydroxyethyl)-Rutosides Systemic and Local Treatment in Chronic Venous Disease and Microangiopathy: An Independent Prospective Comparative Study

O-(beta-hydroxyethyl)-rutosides (HR) is used to treat chronic venous disease and signs and symptoms of chronic venous insufficiency (CVI), varicose veins, and deep venous disease. This independent prospective controlled trial (a registry study) evaluates how the efficacy of HR at the local level (perimalleolar region) can be increased by the administration of a topical HR gel. The study is based on evaluation of microcirculatory variables in patients with severe CVI (ambulatory venous pressure, > 56 mm Hg) and venous microangiopathy. Patients are treated using 1 of the following 3 regimens: oral treatment with 1 g sachets of HR (2 g/d total) plus topical HR 2% gel applied 3 times daily at the internal perimalleolar region; oral treatment only (same dosage), or light elastic compression stockings. Laser Doppler skin flux at rest, skin flux at the perimalleolar region, and transcutaneous PO2 and PCO2 are measured at baseline and at the end of the treatment period. A comparable group of healthy individuals without treatment is observed for 8 weeks. In the treatment groups, flux is increased, PO2 is decreased, and PCO2 is increased compared with normal skin. At 4 and 8 weeks, the improvement in skin flux (which is decreased by all measurements), the increase in PO2, and the decrease in PCO2 (indicating microcirculatory improvement) are statistically significantly greater in the combined oral plus topical treatment group (P < .05). No adverse effects, tolerability problems, or compliance issues are noted. These results indicate an important role of HR in the treatment and control of CVI and venous microangiopathy.

5-Year Control and Treatment of Edema and Increased Capillary Filtration in Venous Hypertension and Diabetic Microangiopathy Using O-(β-Hydroxyethyl)-Rutosides: A Prospective Comparative Clinical Registry

This independent prospective controlled trial evaluates the efficacy of O-(beta-hydroxyethyl)-rutosides (HR) during 5 years of administration against signs and symptoms and further degeneration of microcirculatory disturbances. The protective effect of HR in preventing end-point complications such as venous ulceration is evaluated. This study is based on evaluation of edema and the capillary filtration rate (CFR) in association with a clinical score scale. Patients having a severe degree of chronic venous insufficiency (CVI) and venous microangiopathy and completing at least 5 years of treatment are included. The following 4 groups are considered: group A (patients with CVI but without diabetes mellitus, receiving 1500 mg/d of HR), group B (patients with CVI and diabetes mellitus, receiving 2 g/d of HR), group C (control subjects receiving no pharmacologic or compression treatment), and group D (patients using elastic compression stockings only). All patients received the "best" available treatment. No adverse effects or intolerance is noted, with good compliance (>85%). In group A, there is a statistically significant decrease in the CFR during 5 years of follow-up. In group B, the decrease in the CFR is greater than that in group A. Reductions in edema, swelling, and the CFR during 5 years are notable, and values approach normal levels. During 5 years, HR is effective in treating venous edema and hypertension and in preventing deterioration of the distal venous system. The prevention of ulcerations with HR is another important observation. The effects of HR seem to be partially dose related, and tolerability and compliance are good.

Improvement of Microcirculation and Healing of Venous Hypertension and Ulcers With Crystacide ®: Evaluation With a Microcirculatory Model, Including Free Radicals, Laser Doppler Flux, and PO2/PCO2Measurements

In 32 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of the local application of a hydrogen peroxide cream (Crystacide) applied onto the skin was evaluated using a complex, proportional, microcirculatory model to assess and quantify venous microangiopathy after local treatment. A comparative group treated without Crystacide was included. Laser Doppler flowmetry was used to assess skin perfusion (flux and venoarteriolar response) in association with transcutaneous PO2 and PCO2 measurements. Local plasma free radicals were evaluated in the area surrounding the venous ulcer using the D-Roms test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatments. PO2 was increased (improved, P < .05), and plasma free radicals, PCO2, and laser Doppler flowmetry were decreased (improving toward normal values, P < .05). Also, the ulcerated area was significantly smaller at 10 days in the Crystacide group in comparison with controls (P < .05). In the proportional microcirculatory model, all parameters indicated an important level of improvement significantly larger than in controls. In conclusion, in chronic venous insufficiency and venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals, thus improving healing.

Microcirculatory Effects of Viatromb® Spray Gel Heparin in Chronic Venous Insufficiency: Evaluation of TcPO2 and PCO2—A Product Evaluation Study

The evolution of microcirculatory methods and the definition of the concept of venous microangiopathy allow the study in a quantitative way of microcirculatory changes produced by pharmacologic treatments at the areas most frequently and severely affected by chronic venous insufficiency (CVI), venous hypertensive microangiopathy, and venous ulcerations. This pilot study compares subjects with CVI, in the area most affected by venous hypertension in a 2-week registry. Elastic compression, compression plus Viatromb (lyposomal spray gel heparin), Lioton (gel including heparin), and Viatromb alone were compared. Subjects were evaluated for laser Doppler flux, transcutaneous partial pressure of oxygen (TcPO2), and partial pressure of carbon dioxide (PCO2) and CVI analogic symptom scale. In the Viatromb groups (B and D), significant decreases in laser Doppler flux, PCO2, and CVI score were observed. The decrease was proportionally more important in the elastic compression plus Viatromb group. Partial pressure of oxygen (PO2) was significantly increased. No significant changes were observed in the Lioton group. There was a good effect for compression only. These differences are significant, as they can be observed even in small groups (10-15 patients). No treatment side effects were observed, and compliance and tolerability were very good.

Rapid Relief of Signs/Symptoms in Chronic Venous Microangiopathy With Pycnogenol®: A Prospective, Controlled Study

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd, UK) in patients with severe chronic venous insufficiency. Patients with severe venous hypertension (chronic venous insufficiency, ankle swelling) and history of venous ulcerations were treated with Pycnogenol. Patients received oral Pycnogenol (50 mg capsules, 3 times daily for a total of 150 mg daily) for 8 weeks. A group of 21 patients was included in the treatment group and 18 equivalent patients were observed as controls (no treatment during the observation period). All 21 patients (age 53 years; range, 42-60 years; M:F=11:10) in the treatment group completed the 8-week study. Also the 18 controls completed the follow-up period. There were no drop-outs. The average ambulatory venous pressure was 59.3 (SD 7.2; range 50-68) with a refilling time shorter than 10 seconds (average 7.6; SD 3). There were no differences in ambulatory venous pressure or refilling time between the treatment and control patients. The duration of the disease-from the first signs/symptoms-was on average 5.7 years (SD 2.1). At 4 and 8 weeks, in all Pycnogenol-treated subjects, microcirculatory and clinical evaluations indicated a progressive decrease in skin flux, indicating an improvement in the level of microangiopathy; a significant decrease in capillary filtration; a significant improvement in the symptomatic score; and a reduction in edema. There were no visible effects in controls. In conclusion, this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy. The study indicates the significant clinical role of Pycnogenol in the management, treatment and control of this common clinical problem. The treatment may be also useful to prevent ulcerations by controlling the level of venous microangiopathy.

Comparison of Pycnogenol® and Daflon® in Treating Chronic Venous Insufficiency: A Prospective, Controlled Study

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd., UK) in patients with severe chronic venous insufficiency (CVI) in comparison to the combination of diosmin and hesperidin (Daflon, Servier, France). A group of 86 patients with severe chronic venous insufficiency (CVI), venous hypertension, ankle swelling) and previous history of venous ulcerations received either oral Pycnogenol (capsules) 150 mg or 300 mg daily for 8 weeks or Daflon, 1,000 mg/day. All patients completed the study without dropouts. At the end of the study, microcirculatory results indicated: a progressive decrease of skin flux at rest (RF); a significant decrease in capillary filtration (RAS); an improvement in the symptomatic venous score (ASLS); a reduction in edema; a significant improvement (increase) in pO(2) and a decrease in pCO(2) in the Pycnogenol group. A significant level of improvement was reached after 4 weeks of treatment in most patients (p < .05) of the Pycnogenol group while clinical improvement was significant only in 6 subjects in the Daflon group. The positive effects of treatment with Pycnogenol after 8 weeks were significantly larger in comparison with the Daflon group. In conclusion, this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy and its superiority-considering the evaluated parameters-to the combination of diosmin and hesperidin.

Venoruton® vs Daflon®: Evaluation of Effects on Quality of Life in Chronic Venous Insufficiency

The aim of this independent study was to investigate differences in efficacy between oxerutins (Venoruton) and 500 mg micronized diosmin + hesperidin (D+H) (Daflon) in patients with chronic venous insufficiency (CVI), evaluating venous-related quality of life (Ve-QOL). A first group of 90 patients with severe venous hypertension (CVI, ankle swelling) was randomized to treatment with oxerutins or D+H. The oxerutins group received oral oxerutins (2 g/day); the D+H group received 3 (500 mg) tablets daily every 8 hours for 8 weeks. A second group of 122 comparable patients was included in a registry following the same study format. The 2 treatments were administered with the same methods and procedures. Clinical conditions were comparable. All patients completing 8 weeks of treatment were included in a registry. Specialists or general practitioners included patients when they considered that clinical conditions were compatible with treatment indications using 1 of the 2 treatments on the basis of their evaluation and experience. When cases were compatible with the registry, the prescribing physician communicated the case to our monitoring center. Patients were evaluated without interfering with their treatment. The main target of evaluation for this study was the change in Ve-QOL (range, 0-100) induced by treatment. A specific Ve-QOL questionnaire was used for this study. Ve-QOL score is a specific expression of the changes in QOL induced by CVI in patients between 35 and 75 years old (defined in our population studies) in which no other significant clinical disease is present (as a confounding factor affecting QOL). Two hundred twelve patients completed the 2 parts of the study. The 2 treatment groups were comparable for age and gender distribution. The mean age was 42 years (SD +/-5.5) in the oxerutins group and 41.5 (SD +/-6) in the D+H group. There were no differences in the severity of CVI between the treatment groups at inclusion. A significant decrease (46.8%, p <0.05) in Ve-QOL score; that is, improvement, was observed in the oxerutins group. The change in Ve-QOL was significantly less in the D+H group (15.5%). In conclusion, CVI, venous microangiopathy, and edema were significantly improved by the treatment with oxerutins; the improvement in QOL was significantly greater in the oxerutins group. The comparison with D+H indicates that oxerutins is comparatively more effective on Ve-QOL and on signs/symptoms of CVI.

Malignancy-associated venous thrombosis with concurrent warfarin-induced skin necrosis, venous limb gangrene and thrombotic microangiopathy

Malignancy-associated venous thrombosis with concurrent warfarin-induced skin necrosis, venous limb gangrene and thrombotic microangiopathy -

Chronic Venous Insufficiency

Chronic Venous Insufficiency

HR, 0-(Beta-Hydroxyethyl)-Rutosides; (Venoruton®): Rapid Relief of Signs/Symptoms in Chronic Venous Insufficiency and Microangiopathy: A Prospective, Controlled Study

The aim of this independent study was to demonstrate the rapidity of the clinical action of HR 0-(beta-hydroxyethyl)-rutosides, Venoruton (Novartis Consumer Health) in patients with chronic venous insufficiency (CVI). Two groups of patients with venous hypertension and microangiopathy were treated with HR (1 or 2 g/day, for 8 weeks). Twelve patients (age 56.4; range 44-66; M:F = 6:6) were included in group 1 (1 g/day) (moderate CVI and microangiopathy); 10 patients (age 57.4; range 42-67; M:F = 5:5) in group 2 (2 g/day) with more severe CVI and microangiopathy. Average ambulatory venous pressure (AVP) was 58.6 (range 50-65) with a refilling time (RT) shorter than 10 seconds. There were no significant differences in AVP and RT between the 2 groups, but the duration of the disease was longer in group 2: 3.5 years (SD 2.0) in group 1 and 6.4 years (SD 3.3) in group 2. All included subjects completed the study and no dropouts were observed. In both dose groups there was a progressive decrease in laser Doppler resting flux (RF), indicating improvement in microangiopathy and a significant decrease in capillary filtration (RAS) associated with a significant improvement in analogue scale line score (ASLS) and edema. Although the effect in the 2 g dose group was more rapid on the microcirculatory parameters with a significant effect on RF and RAS after 4 days (effect of 1 g per day after 8 days and 6 days, respectively), there was no difference in the time to onset of a significant clinical improvement (ie, the ASLS and the edema score): 4 days in both groups. Venous microangiopathy and edema were improved by the treatment with HR within a few days. The effects were visible with both dosages, in both severity groups.

HR, 0-(Beta-Hydroxyethyl)-Rutosides, in Comparison with Diosmin+Hesperidin in Chronic Venous Insufficiency and Venous Microangiopathy: An Independent, Prospective, Comparative Registry Study

The aim of this independent study was to investigate differences in efficacy between HR, (0-[beta-hydroxyethyl]-rutosides) and D+H (500 mg, diosmin+hesperidin) in patients with chronic venous insufficiency (CVI). A first group of 90 patients with severe venous hypertension (CVI, ankle swelling) were randomized into an HR or a D+H group. The HR group received oral HR (2 g/day, 8 weeks); the D+H group received a 500 mg tablet 3 times daily for 8 weeks. A second group of comparable patients was included in a registry following the same study format. Patients were openly included; the 2 treatments were administered with the same methods and procedures. Clinical conditions were comparable to those described in the randomized study. Patients treated for at least 8 weeks were included in the registry. A number of physicians (specialists or general practitioners) included patients when they considered that clinical conditions were compatible with using 1 of the 2 treatments on the basis of their personal evaluation and experience. When cases were compatible with the registry, the prescribing physician communicated the case. Patients were evaluated without interfering with the treatment. Main targets of evaluation were skin flux at rest (RF), strain-gauge-derived rate of ankle swelling (RAS), and analogue symptoms score (ASLS). Ninety subjects completed the study in the first group; 122 in the second, registry group (total of 212 patients). The first and second (registry) groups and the 2 treatment groups were comparable for age and sex distribution. The pooled mean age was 42 years (SD +/-5.5) in the HR group (46+62 patients) and 41.5 (SD +/-6) in the D+H group (44+60 patients). Considering pooled data there were no differences in microcirculatory parameters between the pooled treatment groups at inclusion. A significant decrease (p<0.05) in RF and RAS was observed in the HR group at 8 weeks. The decrease in resting skin flux and in capillary filtration was associated with a significant improvement in signs/symptoms (analogue scale line) from an average of 9.4 (range 3-10) to 3.3 (4-6) (p<0.05). Significantly smaller variations were observed in the D+H group. The decrease in RF was 47.6% in the HR group vs 15.7% in the D+H group. The decrease in RAS was 40.9% in the HR group vs 12.8% in the D+H group. The decrease in ASLS was 64.8% in the HR group vs 12.9% in the comparative group. In conclusion venous microangiopathy and edema were improved by the treatment with HR both in the randomized study and in the pooled analysis. The comparison with D+H indicates that HR is comparatively more effective both on microcirculatory parameters and on signs/symptoms of CVI.

Microcirculatory Efficacy of Topical Treatment with Aescin + Essential Phospholipids Gel in Venous Insufficiency and Hypertension: New Clinical Observations

Aescin + essential phospholipids (AEPL) topical gels are used for local treatment of venous and microcirculatory alterations (varicose veins, chronic venous insufficiency). Bruises, swelling, thrombophlebitis, and contusions are effectively treated with AEPL. Active ingredients are escinate and essential phospholipids (EPL). The aim of this new study was the evaluation of the efficacy of the effects of AEPL gel on the microcirculation in subjects with chronic venous insufficiency, venous hypertension (CVH), and venous microangiopathy. Patients were assessed measuring skin flux with laser-Doppler flowmetry (LDF). After 2 weeks of local treatment, all individual values (100%) were significantly decreased (p < 0.05), indicating an improvement in the microcirculation. In all treated patients, flux decreased at least 30% (indicating a decrease in the level of venous microangiopathy) (p < 0.05). Considering these observations, topical treatment with AEPL in areas of venous microangiopathy is beneficial, can prevent ulceration, and improves the skin healing processes.

Microcirculatory efficacy of topical treatment with aescin + essential phospholipids gel on transcutaneous PO2 in venous insufficiency.

A gel including aescin, essential phospholipids (EPL), and heparin (EG) has been used for many years for local treatment of venous, microcirculatory alterations (varicose veins, chronic venous insufficiency). Bruises, swelling, thrombophlebitis, and contusions are effectively treated with this compound. The aim of this study was the evaluation of the efficacy of the effects of an AEPL (aescin+EPL) gel on the microcirculation in subjects with chronic venous insufficiency, venous hypertension (CVH), and venous microangiopathy. Transcutaneous PO(2) was measured at the perimalleolar region. After 2 weeks of treatment, all individual values (100%) were significantly increased (p < 0.05). In all patients, PO(2) increased, indicating a decrease in level of venous microangiopathy. Considering transcutaneous skin PO(2), treatment with AEPL in areas of venous microangiopathy is beneficial in the prevention of ulceration and improves skin healing.

Methods of Evaluation and Quantification of Microangiopathy in High Perfusion Microangiopathy (Chronic Venous Insufficiency and Diabetic Microangiopathy)

Noninvasive macro- and microcirculatory tests provide quantitative information that offers answers to most questions posed in venous diseases. Duplex scanning is used to assess the macrocirculation, and microcirculatory methods are used to assess and quantify venous microangiopathy. Laser Doppler flowmetry is used to assess perfusion. Transcutaneous Po(2) and Pco(2) measurements are used to study venous hypertension, and strain-gauge plethysmography is used to assess capillary filtration. In venous hypertension, fluid filtration into the extracapillary compartment is increased. The increase in filtration is associated with a decreased venoarteriolar response. To quantify capillary filtration, two methods have been developed: venous occlusion plethysmography and rate of ankle swelling. These methods quantify filtration into the extracapillary compartment and, therefore, are an indication of the formation of edema, the most frequent sign in venous hypertension. Other methods, such as the vacuum suction chamber and the edema tester, can be used to assess changes due to treatments in venous hypertension. The techniques described in this article should be used in controlled environmental conditions

Topical Treatment of Venous Microangiopathy in Patients with Venous Ulceration with Essaven Gel

The involvement of the microcirculation in chronic venous insufficiency (CVI), due to venous hypertension, causes venous hypertensive microangiopathy (VHM) and ulceration. VHM is characterized by enlarged, convoluted capillaries; microvascular thrombosis; obliteration of some capillaries; increase in flux, permeability, and edema and altered microlymphatics. PO2 is decreased and CO2 increased. Capillary exchanges are altered and nutritional alterations eventually lead to venous ulcers. Edema is associated with increased capillary pressure, reduced clearance, and increased exchange surface of capillaries, which become tortuous and glomerular-like. The aim of this randomized, placebo-controlled study was to evaluate local treatment with Essaven gel (EG) in subjects with venous microangiopathy and ulcers. Measurements of laser Doppler flux, PO2, and PCO2 in standardized conditions showed positive changes (a significant decrease of the abnormally increased flux and CO2 while PO2 increased) in the EG treatment group. Changes in the placebo and control group were more limited (changes in the placebo group were mainly associated with skin manipulation when placebo-EG was applied). In conclusion, Essaven gel, in comparison with placebo, acutely improves the microcirculation in VHM even with a single acute application.

Methods of Evaluation and Quantification of Microangiopathy in High Perfusion Microangiopathy (Chronic Venous Insufficiency and Diabetic Microangiopathy)

Noninvasive tests have been developed to provide qualitative and quantitative information that can offer answers to most questions posed in venous diseases. While duplex scanning is used to assess the macrocirculation, microcirculatory methods assess and quantify venous microangiopathy. Laser Doppler flowmetry is used to assess tissue viability and perfusion. Transcutaneous PO2 and PCO2 measurements are used to study venous hypertension, and strain-gauge plethysmography (SGP) is used to assess capillary filtration. In venous hypertension fluid filtration into the extracapillary compartment is increased. The increase in filtration is associated with a decreased venoarteriolar response. To quantify capillary filtration two methods have been developed: venous occlusion plethysmography and rate of ankle swelling. These methods quantify filtration into the extracapillary compartment and therefore are an indication of the formation of edema, which is the most frequent sign of venous hypertension. Other methods such as the vacuum suction chamber and the edema tester can be used to assess changes due to treatment in chronic venous hypertension. These methods have been used and validated in several experimental and clinical studies. The techniques described in this article were used in controlled environmental conditions. Results were consistent with clinical problems and data from previous studies from our group and from data from other investigators.

Microcirculatory Effects of Total Triterpenic Fraction of Centella asiatica in Chronic Venous Hypertension: Measurement by Laser Doppler, TcPo2-co2, and Leg Volumetry

The aim of this prospective, randomized study was to demonstrate whether an oral preparation of TTFCA was effective in improving the microcirculation and edema (leg volume) in venous microangiopathy. Forty patients with venous hypertension were included. Treatment was prescribed for 6 weeks (tablets, 60 mg twice daily). Patients were randomized into a treatment and a placebo group. There were 20 patients in each group. In the treatment group the mean age was 42 (SD 7; M:F = 10:10); in the placebo group, the mean age was 40 (SD 9; M:F = 10:10). Tolerability and compliance were very good; there were no dropouts. At inclusion there were no differences between placebo and treatment group. After treatment there was a decrease in resting flux (29%) and an improvement (increase) in venoarteriolar response (52%); PO2 was increased (7.2%) and PCO2 decreased (9.6%). There was an important decrease in leg volume (66 mL decrease; 1.3% volume variation). The difference in flux, O2-CO2 and volume parameters were significant and clinically important at 6 weeks in the treatment group. In conclusion, TTFCA improves microcirculation and leg volume in venous hypertension. The effects of TTFCA are observed even in a limited sample of patients.